Nexplanon

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Nexplanon

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

The following information is based
on experience with either the non-radiopaque etonogestrel implant
(IMPLANON),other progestin-only contraceptives, or experience with combination
(estrogen plus progestin) oral contraceptives.

Complications Of Insertion And Removal

NEXPLANON should be inserted
subdermally so that it will be palpable after insertion, and this should be
confirmed by palpation immediately after insertion. Failure to insert NEXPLANON
properly may go unnoticed unless it is palpated immediately after insertion.
Undetected failure to insert the implant may lead to an unintended pregnancy.
Complications related to insertion and removal procedures, such as pain,
paresthesias, bleeding, hematoma, scarring or infection, may occur.

If NEXPLANON is inserted too
deeply (intramuscular or in the fascia), neural or vascular injury may occur.
To reduce the risk of neural or vascular injury, NEXPLANON should be inserted
at the inner side of the non-dominant upper arm about 8-10 cm (3-4 inches)
above the medial epicondyle of the humerus. NEXPLANON should be inserted
subdermally just under the skin to avoid the large blood vessels and nerves
that lie deeper in the subcutaneous tissues in the sulcus between the triceps
and biceps muscles. Deep insertions of the non-radiopaque etonogestrel implant
(IMPLANON) have been associated with paraesthesia (due to neural injury) and
migration of the implant (due to intramuscular or fascial insertion), and in a
very few cases with intravascular insertion. If infection develops at the
insertion site, start suitable treatment. If the infection persists, the
implant should be removed. Incomplete insertions or infections may lead to
expulsion.

Implant removal may be difficult or impossible if the
implant is not inserted correctly, is inserted too deeply, not palpable,
encased in fibrous tissue, or has migrated. Deep insertions may lead to
difficult localization of the implant and may also result in the need for a
surgical procedure in an operating room in order to remove the implant.
Exploratory surgery without knowledge of the exact location of the implant is
strongly discouraged. Removal of deeply inserted implants should be conducted
with caution in order to prevent injury to deeper neural or vascular structures
in the arm and be performed by healthcare providers familiar with the anatomy
of the arm. Failure to remove the implant may result in continued effects of
etonogestrel, such as compromised fertility, ectopic pregnancy, or persistence
or occurrence of a drug-related adverse event.

Changes In Menstrual Bleeding Patterns

After starting NEXPLANON, women are likely to have a
change from their normal menstrual bleeding pattern. These may include changes
in bleeding frequency (absent, less, more frequent or continuous), intensity
(reduced or increased) or duration. In clinical trials of the non-radiopaque
etonogestrel implant (IMPLANON), bleeding patterns ranged from amenorrhea (1 in
5 women) to frequent and/or prolonged bleeding (1 in 5 women). The bleeding
pattern experienced during the first three months of NEXPLANON use is broadly
predictive of the future bleeding pattern for many women. Women should be
counseled regarding the bleeding pattern changes they may experience so that
they know what to expect. Abnormal bleeding should be evaluated as needed to
exclude pathologic conditions or pregnancy.

In clinical studies of the non-radiopaque etonogestrel
implant, reports of changes in bleeding pattern were the most common reason for
stopping treatment (11.1%). Irregular bleeding (10.8%) was the single most
common reason women stopped treatment, while amenorrhea (0.3%) was cited less
frequently. In these studies, women had an average of 17.7 days of bleeding or
spotting every 90 days (based on 3,315 intervals of 90 days recorded by 780
patients). The percentages of patients having 0, 1-7, 8-21, or > 21 days of
spotting or bleeding over a 90-day interval while using the non-radiopaque
etonogestrel implant are shown in Table 1.

Table 1: Percentages of Patients With 0, 1-7, 8-21, or
> 21 Days of Spotting or Bleeding Over a 90-Day Interval While Using the
Non-Radiopaque Etonogestrel Implant (IMPLANON)

Total Days of Spotting or Bleeding

Percentage of Patients

Treatment Days 91-180
(N = 745)

Treatment Days 271-360
(N = 657)

T reatment Days 631 -720
(N = 547)

0 Days

19%

24%

17%

1-7 Days

15%

13%

12%

8-21 Days

30%

30%

37%

> 21 Days

35%

33%

35%

Bleeding patterns observed with
use of the non-radiopaque etonogestrel implant for up to 2 years, and the
proportion of 90day intervals with these bleeding patterns, are summarized in
Table 2.

Table 2: Bleeding Patterns
Using the Non-Radiopaque Etonogestrel Implant (IMPLANON) During the First 2
Years of UseA

BLEEDING PATTERNS

DEFINITIONS

%B

Infrequent

Less than three bleeding and/or spotting episodes in 90 days (excluding amenorrhea)

33.6

Amenorrhea

No bleeding and/or spotting in 90 days

22.2

Prolonged

Any bleeding and/or spotting episode lasting more than 14 days in 90 days

17.7

Frequent

More than 5 bleeding and/or spotting episodes in 90 days

6.7

A Based on 3315 recording periods of 90 days duration in 780
women, excluding the first 90 days after implant insertion B % = Percentage of 90-day intervals with this pattern

In case of undiagnosed,
persistent, or recurrent abnormal vaginal bleeding, appropriate measures should
be conducted to rule out malignancy.

Ectopic Pregnancies

As with all progestin-only
contraceptive products, be alert to the possibility of an ectopic pregnancy
among women using NEXPLANON who become pregnant or complain of lower abdominal
pain. Although ectopic pregnancies are uncommon among women using NEXPLANON, a
pregnancy that occurs in a woman using NEXPLANON may be more likely to be
ectopic than a pregnancy occurring in a woman using no contraception.

Thrombotic And Other Vascular
Events

The use of combination hormonal
contraceptives (progestin plus estrogen) increases the risk of vascular events,
including arterial events (strokes and myocardial infarctions) or deep venous
thrombotic events (venous thromboembolism, deep venous thrombosis, retinal vein
thrombosis, and pulmonary embolism). NEXPLANON is a progestin-only
contraceptive. It is unknown whether this increased risk is applicable to
etonogestrel alone. It is recommended, however, that women with risk factors
known to increase the risk of venous and arterial thromboembolism be carefully
assessed.

There have been postmarketing reports of serious arterial
and venous thromboembolic events, including cases of pulmonary emboli (some
fatal), deep vein thrombosis, myocardial infarction, and strokes, in women
using the non-radiopaque etonogestrel implant. NEXPLANON should be removed in
the event of a thrombosis.

Due to the risk of thromboembolism associated with
pregnancy and immediately following delivery, NEXPLANON should not be used
prior to 21 days postpartum. Women with a history of thromboembolic disorders
should be made aware of the possibility of a recurrence.

Evaluate for retinal vein thrombosis immediately if there
is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular
lesions.

Consider removal of the NEXPLANON implant in case of
long-term immobilization due to surgery or illness.

Ovarian Cysts

If follicular development occurs, atresia of the follicle
is sometimes delayed, and the follicle may continue to grow beyond the size it
would attain in a normal cycle. Generally, these enlarged follicles disappear
spontaneously. On rare occasion, surgery may be required.

Carcinoma Of The Breast And Reproductive Organs

Women who currently have or have had breast cancer should
not use hormonal contraception because breast cancer may be hormonally
sensitive [seeCONTRAINDICATIONS]. Some studies suggest that the use of
combination hormonal contraceptives might increase the incidence of breast
cancer; however, other studies have not confirmed such findings.

Some studies suggest that the use of combination hormonal
contraceptives is associated with an increase in the risk of cervical cancer or
intraepithelialneoplasia. However, there is controversy about the extent to
which these findings are due to differences in sexual behavior and other
factors.

Women with a family history of breast cancer or who
develop breast nodules should be carefully monitored.

Liver Disease

Disturbances of liver function may necessitate the
discontinuation of hormonal contraceptive use until markers of liver function
return to normal. Remove NEXPLANON if jaundice develops.

Hepatic adenomas are associated with combination hormonal
contraceptives use. An estimate of the attributable risk is 3.3 cases per
100,000 for combination hormonal contraceptives users. It is not known whether
a similar risk exists with progestin-only methods like NEXPLANON.

The progestin in NEXPLANON may be poorly metabolized in
women with liver impairment. Use of NEXPLANON in women with active liver
disease or liver cancer is contraindicated [seeCONTRAINDICATIONS].

Weight Gain

In clinical studies, mean weight gain in U.S.
non-radiopaque etonogestrel implant (IMPLANON) users was 2.8 pounds after one year
and 3.7 pounds after two years. How much of the weight gain was related to the
non-radiopaque etonogestrel implant is unknown. In studies, 2.3% of the users
reported weight gain as the reason for having the non-radiopaque etonogestrel
implant removed.

Elevated Blood Pressure

Women with a history of hypertension-related diseases or
renal disease should be discouraged from using hormonal contraception. For
women with well-controlled hypertension, use of NEXPLANON can be considered.
Women with hypertension using NEXPLANON should be closely monitored. If
sustained hypertension develops during the use of NEXPLANON, or if a
significant increase in blood pressure does not respond adequately to
antihypertensive therapy, NEXPLANON should be removed.

Gallbladder Disease

Studies suggest a small increased relative risk of
developing gallbladder disease among combination hormonal contraceptive users.
It is not known whether a similar risk exists with progestin-only methods like
NEXPLANON.

Carbohydrate And Lipid Metabolic Effects

Use of NEXPLANON may induce mild insulin resistance and
small changes in glucose concentrations of unknown clinical significance.
Carefully monitor prediabetic and diabetic women using NEXPLANON.

Women who are being treated for hyperlipidemia should be
followed closely if they elect to use NEXPLANON. Some progestins may elevate
LDL levels and may render the control of hyperlipidemia more difficult.

Depressed Mood

Women with a history of depressed mood should be
carefully observed. Consideration should be given to removing NEXPLANON in
patients who become significantly depressed.

Return To Ovulation

In clinical trials with the non-radiopaque etonogestrel
implant (IMPLANON), the etonogestrel levels in blood decreased below
sensitivity of the assay by one week after removal of the implant. In addition,
pregnancies were observed to occur as early as 7 to 14 days after removal.
Therefore, a woman should re-start contraception immediately after removal of
the implant if continued contraceptive protection is desired.

Fluid Retention

Hormonal contraceptives may cause some degree of fluid
retention. They should be prescribed with caution, and only with careful
monitoring, in patients with conditions which might be aggravated by fluid
retention. It is unknown if NEXPLANON causes fluid retention.

Contact Lenses

Contact lens wearers who develop visual changes or
changes in lens tolerance should be assessed by an ophthalmologist.

Monitoring

A woman who is using NEXPLANON should have a yearly visit
with her healthcare provider for a blood pressure check and for other indicated
health care.

Drug-Laboratory Test Interactions

Sex hormone-binding globulin concentrations may be
decreased for the first six months after NEXPLANON insertion followed by
gradual recovery. Thyroxine concentrations may initially be slightly decreased
followed by gradual recovery to baseline.

Patient Counseling Information

Counsel women about the insertion and removal procedure
of the NEXPLANON implant. Provide the woman with a copy of the Patient Labeling and ensure that she understands the information in the Patient Labeling before
insertion and removal. A USER CARD and consent form are included in the
packaging. Have the woman complete a consent form and retain it in your
records. The USER CARD should be filled out and given to the woman after
insertion of the NEXPLANON implant so that she will have a record of the
location of the implant in the upper arm and when it should be removed.

Counsel women that NEXPLANON does not protect against HIV
infection (AIDS) or other sexually transmitted diseases.

Counsel women that the use of NEXPLANON may be associated
with changes in their normal menstrual bleeding patterns so that they know what
to expect.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis,
Impairment Of Fertility

In a 24-month carcinogenicity
study in rats with subdermal implants releasing 10 and 20 mcg etonogestrel per
day (equal to approximately 1.8-3.6 times the systemic steady state exposure in
women using NEXPLANON), no drug-related carcinogenic potential was observed.
Etonogestrel was not genotoxic in the in vitro Ames/Salmonella reverse mutation
assay, the chromosomal aberration assay in Chinese hamster ovary cells or in
the in vivo mouse micronucleus test. Fertility in rats returned after
withdrawal from treatment.

Use In Specific Populations

Pregnancy

Teratology studies have been performed in rats and
rabbits using oral administration up to 390 and 790 times the human
etonogestrel dose (based upon body surface), respectively, and revealed no
evidence of fetal harm due to etonogestrel exposure.

Studies have revealed no increased risk of birth defects
in women who have used combination oral contraceptives before pregnancy or
during early pregnancy. There is no evidence that the risk associated with etonogestrel
is different from that of combination oral contraceptives.

NEXPLANON should be removed if maintaining a pregnancy.

Nursing Mothers

Based on limited clinical data, NEXPLANON may be used
during breastfeeding after the fourth postpartum week. Use of NEXPLANON before
the fourth postpartum week has not been studied. Small amounts of etonogestrel
are excreted in breast milk. During the first months after insertion of
NEXPLANON, when maternal blood levels of etonogestrel are highest, about 100 ng
of etonogestrel may be ingested by the child per day based on an average daily
milk ingestion of 658 mL. Based on daily milk ingestion of 150 mL/kg, the mean
daily infant etonogestrel dose one month after insertion of the non-radiopaque
etonogestrel implant (IMPLANON) is about 2.2% of the weight-adjusted maternal
daily dose, or about 0.2% of the estimated absolute maternal daily dose. The
health of breastfed infants whose mothers began using the non-radiopaque
etonogestrel implant during the fourth to eighth week postpartum (n=38) was
evaluated in a comparative study with infants of mothers using a non-hormonal
IUD (n=33). They were breastfed for a mean duration of 14 months and followed
up to 36 months of age. No significant effects and no differences between the
groups were observed on the physical and psychomotor development of these
infants. No differences between groups in the production or quality of breast
milk were detected.

Healthcare providers should discuss both hormonal and
non-hormonal contraceptive options, as steroids may not be the initial choice
for these patients.

Pediatric Use

Safety and efficacy of NEXPLANON have been established in
women of reproductive age. Safety and efficacy of NEXPLANON are expected to be
the same for postpubertal adolescents. However, no clinical studies have been
conducted in women less than 18 years of age. Use of this product before
menarche is not indicated.

Geriatric Use

This product has not been studied in women over 65 years
of age and is not indicated in this population.

Hepatic Impairment

No studies were conducted to evaluate the effect of
hepatic disease on the disposition of NEXPLANON. The use of NEXPLANON in women
with active liver disease is contraindicated [seeCONTRAINDICATIONS].

Renal Impairment

No studies were conducted to evaluate the effect of renal
disease on the disposition of NEXPLANON.

Overweight Women

The effectiveness of the etonogestrel implant in women
who weighed more than 130% of their ideal body weight has not been defined
because such women were not studied in clinical trials. Serum concentrations of
etonogestrel are inversely related to body weight and decrease with time after
implant insertion. It is therefore possible that NEXPLANON may be less
effective in overweight women, especially in the presence of other factors that
decrease serum etonogestrel concentrations such as concomitant use of hepatic
enzyme inducers.

Last reviewed on RxList: 6/13/2014
This monograph has been modified to include the generic and brand name in many instances.